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Cell adaptation to activated FGFR3 includes Sprouty4 up regulation to inhibit the receptor‐mediated ERKs activation from the endoplasmic reticulum
Author(s) -
Lievens Patricia M-J.,
Zanolli Elena,
Garofalo Silvio,
Liboi Elio
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.09.021
Subject(s) - microbiology and biotechnology , endoplasmic reticulum , biology , signal transduction , fibroblast growth factor receptor 3 , receptor , kinase , fibroblast growth factor , biochemistry
The kinase activity of the thanatophoric dysplasia type II–fibroblast growth factor receptor 3 mutant (TDII–FGFR3) hampers its maturation. As a consequence, the immature receptor activates extracellular regulated kinases (ERKs) from the endoplasmic reticulum (ER), which leads to apoptosis. On the other hand, in stable TDII–FGFR3 cells receptor biosynthesis is restored and ERKs are activated from the cell surface. To identify potential mediators of cell adaptation to the activated receptor we investigated gene products that are differently regulated in TDII and wild‐type FGFR3 cells. cDNA representational difference analysis reveals Sprouty4 up regulation in the TDII–FGFR3 cells. Interestingly, Sprouty4 inhibits the TDII–FGFR3‐mediated ERKs activation from the ER, but fails to suppress ERKs activation from cell surface. We conclude that cell adaptation to activated FGFR3 include Sprouty4 activity, which silences the premature receptor signaling and suppress apoptosis.